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Medication

Medication Summary

Discontinuation of the precipitating drug is of paramount importance. Gastrointestinal decontamination is empirically used to minimize systemic absorption of the drug. Hemodialysis may be indicated in certain drug toxicities as well as targeted antitidotal therapies.

Class Summary

GI decontamination with oral activated charcoal is selectively used in the emergency treatment of poisoning caused by some drugs and chemicals.

Activated charcoal (Actidose-Aqua, EZ-Char, Kerr Insta-Char)

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Activated charcoal is used in emergency treatment for poisoning caused by drugs and chemicals. A network of pores adsorbs 100-1000 mg of drug per gram. Multidose charcoal may interrupt enterohepatic recirculation and enhance elimination by enterocapillary exsorption. Theoretically, by constantly bathing the GI tract with charcoal, the intestinal lumen serves as a dialysis membrane for reverse absorption of drug from intestinal villous capillary blood into intestine.

Activated charcoal achieves its maximum effect when administered within 30 minutes after ingestion of a drug or toxin. However, decontamination with activated charcoal may be considered in any patient who presents within 4 hours after the ingestion.

Repeated doses may help to lower systemic levels of ingested compounds, especially sustained-release preparations. Activated charcoal does not dissolve in water. Supply it as an aqueous mixture or in combination with a cathartic (usually sorbitol 70%).

Class Summary

Potassium and magnesium should be repleted in patients taking QTc-prolonging drugs. High doses of magnesium may decrease the risk of QTc prolongation during ibutilide infusions.

Calcium chloride

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Calcium is given to reverse hypotension and improve cardiac conduction defects. Calcium chloride theoretically increases calcium's concentration gradient, overcoming the channel blockade and driving calcium into the cells. It moderates nerve and muscle-performance by regulating action potential excitation threshold.

Magnesium sulfate

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Magnesium acts as an antidysrhythmic agent and diminishes the frequency of premature ventricular contractions (PVCs), particularly those resulting from acute ischemia. Deficiency in this electrolyte can precipitate refractory ventricular fibrillation (VF) and is associated with sudden cardiac death. Magnesium supplementation is used for treatment of torsade de pointes, known or suspected hypomagnesemia, or severe refractory VF.

Sodium bicarbonate (Neut)

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Intravenous sodium bicarbonate can be life saving in patients presenting with cardiotoxicity from antidysrhythmics with sodium-channel blocking properties and QRS widening. Sodium bicarbonate can be given as 1-2 mEq/kg (typically 100 mEq) as a bolus, followed by continuous infusion if the QRS narrows after bolus infusion. A 12-lead EKG should be run while administering the sodium bicarbonate bolus to ensure that QRS narrowing isn't missed because of a delayed EKG. Serum pH should be monitored if a sodium bicarbonate infusion is used.

Class Summary

Vasopressors are indicated for persistent hypotension not responsive to judicious fluid loading and sodium bicarbonate.

Norepinephrine (Levophed)

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Norepinephrine has strong beta1- and alpha-adrenergic effects and moderate beta2 effects, which increase cardiac output, blood pressure, and heart rate, while decreasing renal perfusion and pulmonary vascular resistance

Class Summary

These agents may be used to treat symptomatic arrhythmia.

Isoproterenol (Isuprel)

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Isoproterenol is used to treat torsade de pointes if magnesium supplementation fails to treat it. It is also used to treat ventricular tachycardia or fibrillation in the setting of Brugada syndrome.

Class Summary

By increasing the action of gamma aminobenzoic acid (GABA), a major inhibitory neurotransmitter, benzodiazepines may depress all levels of the central nervous system (CNS), including the limbic system and the reticular formation.

Diazepam (Valium, Diastat)

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Diazepam depresses all levels of the CNS (eg, limbic system and reticular formation), possibly by increasing the activity of GABA. It is a third-line agent for agitation or seizures because of its shorter duration of anticonvulsive effects and the accumulation of active metabolites that may prolong sedation.

Lorazepam (Ativan)

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Lorazepam is the drug of choice for treatment of status epilepticus because persists in the CNS longer than diazepam. The rate of injection should not exceed 2 mg/min. This agent may be administered intramuscularly if vascular access cannot be obtained.

Midazolam

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Midazolam is an alternative agent for termination of refractory status epilepticus. Compared with diazepam, midazolam has twice the affinity for benzodiazepine receptors; however, because it is water soluble, midazolam takes approximately 3 times longer than diazepam to achieve peak electroencephalographic effects. Thus, the clinician must wait 2-3 minutes to fully evaluate sedative effects before initiating a procedure or repeating the dose. This agent may be administered intramuscularly if vascular access cannot be obtained.

Duncan WJ, Tyrrell MJ, Bharadwaj BB. Disopyramide as a negative inotrope in obstructive cardiomyopathy in children. Can J Cardiol. 1991 Mar. 7 (2):81-6. [QxMD MEDLINE Link].
Atkinson AJ Jr, Krumlovsky FA, Huang CM, del Greco F. Hemodialysis for severe procainamide toxicity: clinical and pharmacokinetic observations. Clin Pharmacol Ther. 1976 Nov. 20(5):585-92. [QxMD MEDLINE Link].
Mok NS, Chan NY, Chiu AC. Successful use of quinidine in treatment of electrical storm in Brugada syndrome. Pacing Clin Electrophysiol. 2004 Jun. 27 (6 Pt 1):821-3. [QxMD MEDLINE Link].
Mladěnka P, Applová L, Patočka J, Costa VM, Remiao F, Pourová J, et al. Comprehensive review of cardiovascular toxicity of drugs and related agents. Med Res Rev. 2018 Jul. 38 (4):1332-1403. [QxMD MEDLINE Link]. [Full Text].
Collinsworth KA, Kalman SM, Harrison DC. The clinical pharmacology of lidocaine as an antiarrhythymic drug. Circulation. 1974 Dec. 50 (6):1217-30. [QxMD MEDLINE Link].
Napolitano C, Bloise R, Priori SG. Gene-specific therapy for inherited arrhythmogenic diseases. Pharmacol Ther. 2006 Apr. 110 (1):1-13. [QxMD MEDLINE Link].
Kusumoto M, Ueno K, Oda A, Takeda K, Mashimo K, Takaya K, et al. Effect of fluvoxamine on the pharmacokinetics of mexiletine in healthy Japanese men. Clin Pharmacol Ther. 2001 Mar. 69 (3):104-7. [QxMD MEDLINE Link].
Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991 Mar 21. 324 (12):781-8. [QxMD MEDLINE Link].
Priori SG, Napolitano C, Schwartz PJ, Bloise R, Crotti L, Ronchetti E. The elusive link between LQT3 and Brugada syndrome: the role of flecainide challenge. Circulation. 2000 Aug 29. 102 (9):945-7. [QxMD MEDLINE Link].
Siu CW, Wong MP, Ho CM, Lam CL, Tse HF. Fatal lung toxic effects related to dronedarone use. Arch Intern Med. 2012 Mar 26. 172 (6):516-7. [QxMD MEDLINE Link].
Tschuppert Y, Buclin T, Rothuizen LE, Decosterd LA, Galleyrand J, Gaud C, et al. Effect of dronedarone on renal function in healthy subjects. Br J Clin Pharmacol. 2007 Dec. 64 (6):785-91. [QxMD MEDLINE Link].
Saarimaa H. Combination of clonidine and sotalol in hypertension. Br Med J. 1976 Apr 3. 1 (6013):810. [QxMD MEDLINE Link].
Frick M, Darpö B, Ostergren J, Rosenqvist M. The effect of oral magnesium, alone or as an adjuvant to sotalol, after cardioversion in patients with persistent atrial fibrillation. Eur Heart J. 2000 Jul. 21 (14):1177-85. [QxMD MEDLINE Link].
Somberg JC, Preston RA, Ranade V, Cvetanovic I, Molnar J. Gender differences in cardiac repolarization following intravenous sotalol administration. J Cardiovasc Pharmacol Ther. 2012 Mar. 17(1):86-92. [QxMD MEDLINE Link].
Nair M, George LK, Koshy SK. Safety and efficacy of ibutilide in cardioversion of atrial flutter and fibrillation. J Am Board Fam Med. 2011 Jan-Feb. 24 (1):86-92. [QxMD MEDLINE Link].
Singh S, Zoble RG, Yellen L, Brodsky MA, Feld GK, Berk M, et al. Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study. Circulation. 2000 Nov 7. 102 (19):2385-90. [QxMD MEDLINE Link].
Gummin DD, Mowry JB, Beuhler MC, Spyker DA, Bronstein AC, Rivers LJ, et al. 2020 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 38th Annual Report. Clin Toxicol (Phila). 2021 Dec. 59 (12):1282-1501. [QxMD MEDLINE Link]. [Full Text].
Zitnik, RJSO. Drug-induced lung disease: Antiarrhythmic agents. J Respir Dis. 1996. 17:254.
Venkayya RV, Poole RM, Pentz WH. Respiratory failure from procainamide-induced myopathy. Ann Intern Med. 1993 Aug 15. 119 (4):345-6. [QxMD MEDLINE Link].
Godley PJ, Morton TA, Karboski JA, Tami JA. Procainamide-induced myasthenic crisis. Ther Drug Monit. 1990 Jul. 12 (4):411-4. [QxMD MEDLINE Link].
Cohen IS, Jick H, Cohen SI. Adverse reactions to quinidine in hospitalized patients: findings based on data from the Boston Collaborative Drug Surveillance Program. Prog Cardiovasc Dis. 1977 Sep-Oct. 20 (2):151-63. [QxMD MEDLINE Link].
Mintzer J, Burns A. Anticholinergic side-effects of drugs in elderly people. J R Soc Med. 2000 Sep. 93 (9):457-62. [QxMD MEDLINE Link].
Somberg JC, Timar S, Bailin SJ, Lakatos F, Haffajee CI, Tarjan J, et al. Lack of a hypotensive effect with rapid administration of a new aqueous formulation of intravenous amiodarone. Am J Cardiol. 2004 Mar 1. 93 (5):576-81. [QxMD MEDLINE Link].
Lindquist DE, Rowe AS, Heidel E, Fleming T, Yates JR. Evaluation of the Hemodynamic Effects of Intravenous Amiodarone Formulations During the Maintenance Phase Infusion. Ann Pharmacother. 2015 Dec. 49 (12):1317-21. [QxMD MEDLINE Link].
Nacca N, Bhamidipati CM, Yuhico LS, Pinnamaneni S, Szombathy T. Severe amiodarone induced pulmonary toxicity. J Thorac Dis. 2012 Dec. 4 (6):667-70. [QxMD MEDLINE Link].
Ernawati DK, Stafford L, Hughes JD. Amiodarone-induced pulmonary toxicity. Br J Clin Pharmacol. 2008 Jul. 66 (1):82-7. [QxMD MEDLINE Link].
Vorperian VR, Havighurst TC, Miller S, January CT. Adverse effects of low dose amiodarone: a meta-analysis. J Am Coll Cardiol. 1997 Sep. 30 (3):791-8. [QxMD MEDLINE Link].
Orr CF, Ahlskog JE. Frequency, characteristics, and risk factors for amiodarone neurotoxicity. Arch Neurol. 2009 Jul. 66 (7):865-9. [QxMD MEDLINE Link].
Køber L, Torp-Pedersen C, McMurray JJ, et al. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med. 2008 Jun 19. 358(25):2678-87. [QxMD MEDLINE Link].
Danielly J, DeJong R, Radke-Mitchell LC, Uprichard AC. Procainamide-associated blood dyscrasias. Am J Cardiol. 1994 Dec 1. 74 (11):1179-80. [QxMD MEDLINE Link].
Hudson CJ, Whitner TE, Rinaldi MJ, Littmann L. Brugada electrocardiographic pattern elicited by inadvertent flecainide overdose. Pacing Clin Electrophysiol. 2004 Sep. 27(9):1311-3. [QxMD MEDLINE Link].
Thevenin J, Da Costa A, Roche F, Romeyer C, Messier M, Isaaz K. Flecainide induced ventricular tachycardia (torsades de pointes). Pacing Clin Electrophysiol. 2003 Sep. 26 (9):1907-8. [QxMD MEDLINE Link].
Odeh M, Seligmann H, Oliven A. Propafenone-induced ataxia: report of three cases. Am J Med Sci. 2000 Aug. 320 (2):151-3. [QxMD MEDLINE Link].
MacNeil DJ, Davies RO, Deitchman D. Clinical safety profile of sotalol in the treatment of arrhythmias. Am J Cardiol. 1993 Aug 12. 72(4):44A-50A. [QxMD MEDLINE Link].
Merola JF. Lupus-like syndromes related to drugs. Schur PH, Massarotti E. Lupus Erythematosus: Clinical Evaluation and Treatment. New York: Springer; 211-221.
[Guideline] Goldschlager N, Epstein AE, Naccarelli G, Olshansky B, Singh B. Practical guidelines for clinicians who treat patients with amiodarone. Practice Guidelines Subcommittee, North American Society of Pacing and Electrophysiology. Arch Intern Med. 2000 Jun 26. 160 (12):1741-8. [QxMD MEDLINE Link].
Richer M, Robert S. Fatal hepatotoxicity following oral administration of amiodarone. Ann Pharmacother. 1995 Jun. 29 (6):582-6. [QxMD MEDLINE Link].
Gowda RM, Khan IA, Wilbur SL, Vasavada BC, Sacchi TJ. Torsade de pointes: the clinical considerations. Int J Cardiol. 2004 Jul. 96 (1):1-6. [QxMD MEDLINE Link].
Tzivoni D, Keren A, Stern S, Gottlieb S. Disopyramide-induced Torsade de Pointes. Arch Intern Med. 1981 Jun. 141 (7):946-7. [QxMD MEDLINE Link].
Arimori K, Kawano H, Nakano M. Gastrointestinal dialysis of disopyramide in healthy subjects. Int J Clin Pharmacol Ther Toxicol. 1989 Jun. 27 (6):280-4. [QxMD MEDLINE Link].
Holt DW, Helliwell M, O'Keeffe B, Hayler AM, Marshall CB, Cook G. Successful management of serious disopyramide poisoning. Postgrad Med J. 1980 Apr. 56 (654):256-60. [QxMD MEDLINE Link].
Neal JM, Woodward CM, Harrison TK. The American Society of Regional Anesthesia and Pain Medicine Checklist for Managing Local Anesthetic Systemic Toxicity: 2017 Version. Reg Anesth Pain Med. 2018 Feb. 43 (2):150-153. [QxMD MEDLINE Link].
Mazoit JX, Le Guen R, Beloeil H, Benhamou D. Binding of long-lasting local anesthetics to lipid emulsions. Anesthesiology. Feb 2009. 110(2):380-6. [QxMD MEDLINE Link].
Akinci E, Yüzbasioglu Y, Coskun F. Hemodialysis as an alternative treatment of mexiletine intoxication. Am J Emerg Med. 2011 Nov. 29(9):1235.e5-6. [QxMD MEDLINE Link].
Ellsworth H, Stellpflug SJ, Cole JB, Dolan JA, Harris CR. A life-threatening flecainide overdose treated with intravenous fat emulsion. Pacing Clin Electrophysiol. 2013 Mar. 36(3):e87-9. [QxMD MEDLINE Link].
Khatiwada P, Clark L, Khunger A, Rijal BB, Ritter J. A Case Report of Flecainide Toxicity With Review of Literature. Cureus. 2022 Feb. 14 (2):e22261. [QxMD MEDLINE Link].
Bologa C, Lionte C, Popescu A, Sorodoc V, Sorodoc L. First Case of Acute Poisoning with Amiodarone and Flecainide in Attempted Suicide Successfully Managed with Lipid Emulsion Therapy in the Emergency Department: Case Report and Literature Review. Healthcare (Basel). 2021 Jun 4. 9 (6):[QxMD MEDLINE Link]. [Full Text].
Auzinger GM, Scheinkestel CD. Successful extracorporeal life support in a case of severe flecainide intoxication. Crit Care Med. 2001 Apr. 29(4):887-90. [QxMD MEDLINE Link].
Qamar S, Hassan W, Sra J, Akhtar M, Mortada ME. Abstract 14890: Hyponatremia Associated with Flecainide: Case Series. Circulation. 2012. 126.21:[Full Text].
Khavandi A, Walker. Flecainide cardiotoxicity precipitated by electrolyte imbalance. Caution with thiazide diuretics. Emerg Med J. 2007. 24(5):[QxMD MEDLINE Link].
Wozakowska-Kaplon B, Stepien-Walek A. Propafenone overdose: cardiac arrest and full recovery. Cardiol J. 2010. 17(6):619-22. [QxMD MEDLINE Link].
Ovaska H, Ludman A, Spencer EP, Wood DM, Jones AL, Dargan PI. Propafenone poisoning--a case report with plasma propafenone concentrations. J Med Toxicol. 2010 Mar. 6 (1):37-40. [QxMD MEDLINE Link].
Patsilinakos S, Christou A, Kafkas N, Nikolaou N, Antonatos D, Katsanos S, et al. Effect of high doses of magnesium on converting ibutilide to a safe and more effective agent. Am J Cardiol. 2010 Sep 1. 106 (5):673-6. [QxMD MEDLINE Link].
Jovic-Stosic J, Gligic B, Putic V, Brajkovic G, Spasic R. Severe propranolol and ethanol overdose with wide complex tachycardia treated with intravenous lipid emulsion: a case report. Clin Toxicol (Phila). 2011 Jun. 49(5):426-30. [QxMD MEDLINE Link].
Montiel V, Gougnard T, Hantson P. Diltiazem poisoning treated with hyperinsulinemic euglycemia therapy and intravenous lipid emulsion. Eur J Emerg Med. 2011 Apr. 18(2):121-3. [QxMD MEDLINE Link].
French D, Armenian P, Ruan W, Wong A, Drasner K, Olson KR, et al. Serum verapamil concentrations before and after Intralipid® therapy during treatment of an overdose. Clin Toxicol (Phila). 2011 Apr. 49(4):340-4. [QxMD MEDLINE Link].
French D, Smollin C, Ruan W, Wong A, Drasner K, Wu AH. Partition constant and volume of distribution as predictors of clinical efficacy of lipid rescue for toxicological emergencies. Clin Toxicol (Phila). 2011 Nov. 49(9):801-9. [QxMD MEDLINE Link].
Martindale JL, Brown DFM. Rapid Interpretation of ECGs in Emergency Medicine: A Visual Guide. Lippincott Williams and Wilkins; 2012.
EM Williams. Classifying antiarrhythmic actions: by facts or speculation. The Journal of Clinical Pharmacology. 1992 Nov. 32:964–77. [QxMD MEDLINE Link].
Lim YP, Lin CL, Lin YN, Ma WC, Chen WC, Hung DZ, et al. Antiarrhythmic agents and the risk of malignant neoplasm of liver and intrahepatic bile ducts. PLoS One. 2015. 10 (1):e0116960. [QxMD MEDLINE Link].
Benowitz NL. Antiarrhythmic Drugs. Olson KR. Poisoning & Drug Overdose. 6th. Mcgraw-Hill; 2012.
Piña IL, Oghlakian G. Adverse Cardiovascular Drug Interactions and Complications. Fuster V, Walsh RA, Harrington RA. Hurst's The Heart. 13th. Mcgraw-Hill; 2011.
Benowitz NL. Quinidine and Other Type Ia Antiarrhythmic Drugs. Olson KR. Poisoning & Drug Overdose. 6th ed. McGraw-Hill; 2012.
Trevor AJ, Katzung BG, Kruidering-Hall. Antiarrhythmic Drugs. Trevor AJ, Katzung BG, Kruidering-Hall. Katzung & Trevor's Pharmacology: Examination & Board Review,. 11th ed. McGraw-Hill; 2015.
Frishman WH, Alwarshetty M. Beta-adrenergic blockers in systemic hypertension: pharmacokinetic considerations related to the current guidelines. Clin Pharmacokinet. 2002. 41 (7):505-16. [QxMD MEDLINE Link].
Ting SM, Lee D, Maclean D, Sheerin NS. Paranoid psychosis and myoclonus: flecainide toxicity in renal failure. Cardiology. 2008. 111 (2):83-6. [QxMD MEDLINE Link].
Gentzkow GD, Sullivan JY. Extracardiac adverse effects of flecainide. Am J Cardiol. 1984 Feb 27. 53 (5):101B-105B. [QxMD MEDLINE Link].
Tsuchishita Y, Fukumoto K, Kusumoto M, Ueno K. Effects of serum concentrations of disopyramide and its metabolite mono-N-dealkyldisopyramide on the anticholinergic side effects associated with disopyramide. Biol Pharm Bull. 2008 Jul. 31 (7):1368-70. [QxMD MEDLINE Link].

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ECG in a patient who ingested 4 of flecainide. QRS = 200 milliseconds; QTc = 585 milliseconds. Used with permission from Lippincott, Williams & Wilkins (in Martindale JL, Brown DFM. Rapid Interpretation of ECGs in Emergency Medicine: A Visual Guide. Lippincott Williams and Wilkins; 2012).
Schematic of the cardiac action potential. Phase 0 depicts the the influx of sodium ions. Phases 1 and 3 correspond to the sodium-channel inactivation and the repolarizing eflux of potassium ions, respectively. Phase 2 depicts the opening of voltage-sensitive calcium channels causing a plateau in voltage.

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Author

Nidhish Sasi, MD Resident Physician, Department of Emergency Medicine, Kings County Hospital Center, State University of New York Downstate Medical Center

Nidhish Sasi, MD is a member of the following medical societies: American Medical Association, American College of Emergency Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Sage W Wiener, MD Assistant Professor, Department of Emergency Medicine, State University of New York Downstate Medical Center; Director of Medical Toxicology, Department of Emergency Medicine, Kings County Hospital Center

Sage W Wiener, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Michael A Miller, MD Clinical Professor of Emergency Medicine, Medical Toxicologist, Department of Emergency Medicine, Texas A&M Health Sciences Center; CHRISTUS Spohn Emergency Medicine Residency Program

Michael A Miller, MD is a member of the following medical societies: American College of Medical Toxicology

Disclosure: Nothing to disclose.

Additional Contributors

Jennifer L Martindale, MD Clinical Assistant Professor, Department of Emergency Medicine, Kings County Hospital, State University of New York Downstate Medical Center

Disclosure: Nothing to disclose.

Denise Ammon, MD, MA Resident Physician, Department of Emergency Medicine, Kings County Hospital, State University of New York Downstate Medical Center

Denise Ammon, MD, MA is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, American Medical Student Association/Foundation, American Society of Anesthesiologists, Emergency Medicine Residents' Association

Disclosure: Nothing to disclose.

Acknowledgements

Michael J Burns, MD Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center

Michael J Burns, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine